Understanding K ^trans: a simulation study based on a multiple-pathway model

The transfer constant K ^trans is commonly employed in dynamic contrast-enhanced MRI studies, but the utility and interpretation of K ^trans as a potential biomarker of tumor vasculature remains unclear. In this study, computer simulations based on a comprehensive tracer kinetic model with multiple pathways was used to provide clarification on the interpretation and application of K ^trans. Tissue concentration-time curves pertaining to a wide range of transport conditions were simulated using the multiple-pathway (MP) model and fitted using the generalized kinetic (GK) and extended GK models. Relationships between K ^trans and plasma flow F _p, vessel permeability PS and extraction rate EF _p under various transport conditions were assessed by correlation and regression analysis. Results show that the MP model provides an alternative two-tier interpretation of K ^trans based on the vascular transit time. K ^trans is primarily associated with F _p and EF _p respectively, in the slow and rapid vascular transit states, independent of the magnitude of PS. The relative magnitudes of PS and F _p only serve as secondary constraints for which K ^trans can be further associated with EF _p and PS in the slow and rapid transit states, respectively.